Diosmetin: A dietary flavone as modulator of signaling pathways in cancer progression

Abstract Flavonoids, constituting the most extensive category of polyphenols, founds in a variety of plants and comprise over 9000 compounds. Diosmetin, O‐methylated flavone (3’,5,7‐trihydroxy‐4’‐methoxyflavone) of flavonoid aglycone diosmin have witnessed a significant surge in recent years. Many studies showed that flavonoids induced cytotoxicity in different organ specific cancer types. Thus, current review evaluates the anticancer potential of diosmetin and shed light on its mechanism of action such as cell cycle regulation, apoptosis via both intrinsic and extrinsic pathway, autophagy and tumour progression and metastasis. It also provides comprehensive analysis of different cancer targets and their role in breast, colon, hepatic, gliomas, leukemia, lung, prostate and skin cancer. Combination studies of diosmetin to improve drug sensitivity and reduce toxicity towards normal cells has been also discussed. Besides, in vitro studies, present review also discuss the anticancer potential of diosmetin on xenograft mice model. Different natural sources of diosmetin, limitations, pharmacokinetic analysis and toxicity study also summarized in current review. The emphasis on enhancing solubility and permeability for clinical utility has been thoroughly highlighted with particular attention given to the utilization of nano formulations to overcome existing barriers. At last, in‐depth analysis of current challenges and a forward‐looking perspective deliberated to address the existing gaps and position it as a promising lead compound for clinical applications in cancer treatment. This discussion is boosted by diosmetin's potential anticancer properties on different cancers, makes valuable candidates in the ongoing quest for effective therapeutic interventions against cancer.